Sickle cell disease is a generic term for a group of genetic disorders that affect not only African-Americans, but other ethnic groups as well. It is hypothesized that glycophorin may be altered is sickle cell disease. Glycophorin is one of the best studied mammalian integral membrane proteins, and yet, very little is known regarding its function or gene expression in either normal or sickled cells. Herein, we propose (1) to ascertain topographical patterns of human glycophorin in normal and sickle RBC using antibodies to determine preferential expression of any of the glycophorin types; (2) to determine variances in glycophorin messenger RNA levels between normal red cells (HbAA) and the variants of HbS, including HbSS, HbSC and HbS with beta-thalassemia combination of sickle cell diseased red cells; (3) to identify glycophorin A and glycophorin C genes; (4) to define the exact DNA sequence(s) responsible for the RFLP by determining the DNA sequence of subcloned fractions; and (5) to relate the identified RFLP of glycophorin to hypothetical functional properties of glycophorin in normal erythrocyte physiology. Overall, our goal is to establish more detailed information on the basic biology of glycophorin as a red cell membrane protein.